This project is a comprehensive study of cilia, particularly investigating the mechanisms of motility and its control. The source of force generation in these organelles is a sliding interaction between adjacent axonemal doublet microtubules mediated by the hynein-1 arms that bridge the doublets. The dynein-1 arms can be visualized in negative stain electron microscopy and the direction of sliding can be defined. We plan to characterize the sliding interaction more completely in terms of (1) changes in arm morphology (2) effects of inhibitors (3) the mechanochemical cycle, including feedback mechanisms which cause asynchronous sliding and (4) the effects of Ca 2 ions on sliding. Since cilia are important to maintenance of normal function respiratory epithelia, among others, these studies may give fundamental information useful in examining loss of motility after treatment of such epithelia with specific agents and in genetic disease.